Taxanes, represented by paclitaxel, docetaxel and the like, are anti-cancerous alkaloids, mainly contained in plants such as yew trees, or derivatives thereof. In general, the taxanes have an extremely poor solubility in water, and therefore research to impart water-solubility to the taxanes has been conducted.
For example, Patent Document 1 and Patent Document 2 describe polymeric derivatives of paclitaxel bound to polyethylene glycol as a prodrug.
However, in these polymeric derivatives of paclitaxel, only one or two paclitaxel molecules can be bound to one molecule of polyethylene glycol, and as a result, a large amount of the polymer is required for the administration of an effective amount of the drug.
Furthermore, Patent Document 3 describes a derivative in which polyglutamic acid is bound to an alcoholic hydroxyl group of paclitaxel or docetaxel. However, no description is given on a polymeric derivative in which a taxane is bound to a polymer having a polyethylene glycol moiety and two or more succinic acid monoamide moieties.
Patent Document 4 describes a molecule in which a drug is bound to a block copolymer of polyethylene glycol and polyaspartic acid, and the molecule forms micelles and has water solubility. Patent Document 5 describes a polymeric carrier in which a hydrophobic substance is bound to a carboxylic acid group in a side chain of a block copolymer of polyethylene glycol and poly(acidic amino acid), as a carrier functioning as a polymeric drug carrier. Patent Document 6 describes a polymer derivative of camptothecins, in which a carboxylic acid group in a side chain of a block copolymer of polyethylene glycols and polyglutamic acid is bound to a phenolic hydroxyl group of the camptothecins. However, none of Patent Documents 4 to 6 refers to conjugates of taxanes.
Patent Document 1: International Publication No. WO 93/24476 Pamphlet
Patent Document 2: Japanese Patent Application Laid Open (KOKAI) No. 10-513187
Patent Document 3: Japanese Patent Application Laid Open (KOHYO) No. 2003-511423
Patent Document 4: Japanese Patent No. 2694923
Patent Document 5: Japanese Patent No. 3268913
Patent Document 6: International Publication No. WO 2004/39869 Pamphlet